Allergen immunotherapy (AIT) is an approved treatment for seasonal respiratory allergic diseases. A depigmented polymerized birch pollen extract for subcutaneous allergen immunotherapy (SCIT) has been demonstrated to be efficacious and safe in patients allergic to birch pollen and its homologous group.

To determine whether SCIT with a birch pollen formulation (5000 depigmented polymerized (DPP) units/mL) shows sustained and long‐term efficacy in adults and adolescents with birch‐pollen induced allergic rhinitis with or without intermittent asthma.

A multicentre (n = 66), double‐blind, placebo‐controlled Phase III clinical trial was performed in the Czech Republic, Finland, Germany, Latvia, Lithuania, Poland and Russia. Participants were randomized 2:1 to active treatment (birch 5000 DPP/ml) or placebo for three years of SCIT and followed up for two treatment‐free years. The primary efficacy endpoint was the EAACI's combined symptom and medication score for rhinoconjunctivitis (CSMSEAACI).

A total of 973 participants were screened and 649 were randomized (active treatment: n = 434; placebo: n = 215). The intention‐to‐treat analysis of the CSMSEAACI in the overall study population did not demonstrate statistically significant differences in years 1, 2 and 3. In a post‐hoc analysis, among the subgroup of patients monosensitized to birch pollen allergen only (n = 200), we observed a statistically significant difference (active treatment vs. placebo) in the CSMSEAACI in year 2, 3 and 5. The AIT's safety profile was good.

SCIT with a depigmented polymerized birch pollen extract was safe. Sustained and long‐term efficacy in years 2, 3 and 5 in monosensitized patients, but not in polysensitized patients was demonstrated. (EudraCT 2012‐000414‐11).

Thymic stromal lymphopoietin (TSLP) has been shown to play a central role in the initiation and persistence of allergic responses.

We evaluated whether tezepelumab, a human monoclonal anti-TSLP antibody, improved the efficacy of subcutaneous allergen immunotherapy (SCIT) and promoted the development of tolerance in patients with allergic rhinitis.

We conducted a double-blind parallel design trial in patients with cat allergy. A total of 121 patients were randomized to receive either intravenous tezepelumab plus subcutaneous cat SCIT, cat SCIT alone, tezepelumab alone, or placebo for 52 weeks followed by 52 weeks of observation. Nasal allergen challenges (NAC), skin testing, and blood and nasal samples were obtained throughout the study.

At week 52, the NAC-induced total nasal symptom scores (TNSS) (calculated as an area-under-the-curve [AUC 0-1 hr] and as a peak score [peak 0-1 hr] during the first hour after nasal allergen challenge) were significantly reduced in patients receiving tezepelumab/SCIT compared with SCIT alone. At week 104, one year after stopping treatment, the primary endpoint TNSS AUC 0-1hr was not significantly different in the tezepelumab/SCIT group compared to SCIT alone, while TNSS peak 0-1 hr was significantly lower in those receiving combination treatment vs. SCIT. Transcriptomic analysis of nasal epithelial samples demonstrated that treatment with the combination of SCIT/tezepelumab, but neither monotherapy, caused persistent downregulation of a gene network related to type 2 inflammation which was associated with improvement in NAC responses.

These results suggest that inhibition of TSLP augments the efficacy of SCIT during therapy and may promote tolerance following a one year course of treatment. (ClinicalTrials.gov Identifier: NCT02237196).

The European Academy of Allergy and Clinical Immunology recommended the Combined Symptom and Medication Score (CSMS) as primary endpoint in clinical trials on allergen-specific immunotherapy (AIT) in allergic rhinoconjunctivitis. Here, the correlation between the CSMS and the validated standardised Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ(S)), Rhinitis Control Assessment Test (RCAT) and Visual Analogue Scale (VAS) was analysed.

Two prospective, multicentre, non-interventional studies on tree pollen, grass pollen and house dust mite allergic patients were performed. The first study comprised 167 patients receiving AIT (AIT population), and the second included 56 patients treated with symptomatic medication only (control population). For up to two seasons (pollen)/exposure periods (house dust mites), participants documented their symptoms and medication intake in a CSMS diary, including VAS. In addition, the standardised RQLQ(S) and the RCAT were completed during study visits.

Comparison between CSMS and RQLQ(S) revealed a positive correlation in the AIT population (r = 0.426) and in the control population (r = 0.569). For CSMS and RCAT, a negative correlation with r = -0.409 (AIT) and r = -0.547 (control) was shown. Positive correlation between CSMS and VAS was also demonstrated with r = 0.585 (AIT) and r = 0.563 (control).

These results support the assumption that the CSMS correlates with quality of life, symptom severity and symptom control on the one hand, while the moderate strength of correlations on the other hand mirrors distinctions of the CSMS compared to the assessments used here.

Cow's milk allergy (CMA) is the most common allergy in infants that decreases the quality of life of patients and their families. Standard treatment for CMA is the strict avoidance of milk; new treatment strategies such as oral immunotherapy (OIT) have been sought for patients with CMA. We aimed to assess the clinical efficacy and safety of OIT in the treatment of children with immunoglobulin E-mediated CMA (IMCMA).

We searched all randomized controlled trials in which OIT is used to treat children with IMCMA from five international electronic databases. We estimated a pooled risk ratio (RR) for each outcome using a Mantel-Haenzel fixed-effects model if statistical heterogeneity was low.

Eleven studies were chosen for meta-analysis, including a total of 469 children (242 OITs, 227 controls). One hundred and seventy-six patients (72.7%) in the OIT were desensitized compared with 49 patients (21.6%) in the control group (RR: 7.35, 95% confidence interval (CI): 2.82-19.13, p < .0001). The desensitization effect of OIT was particularly significant in children over 3 years old (RR: 18.05, 95% CI: 6.48-50.26, p < .00001). Although adverse effects were common, they usually involved mild reactions, but epinephrine use was more common in the OIT group (RR: 7.69, 95% CI: 2.16-27.33, p < .002).

OIT can lead to desensitization in the majority of individuals with IMCMA, especially in patients over 3 years old. A major problem of OIT is the frequency of adverse events, although most are mild. OIT may be an alternative treatment in the future.

Oral immunotherapy (OIT) is an emerging method for treating food allergy in children. However, data regarding adults undergoing this process are lacking.

We retrospectively analyzed the medical records of patients with food allergy aged ≥17 years who completed OIT treatment between April 2010 and December 2020 at Shamir Medical Center. Data were compared with that of children aged 4 to <11 years and adolescents aged ≥11 to 17 treated during the same time period.

A total of 96 adults at a median age of 22.3 years who underwent OIT for milk (n = 53), peanut ( n = 18), sesame ( n = 7), egg ( n = 5), and tree nuts (n = 13) were analyzed and compared with 1299 children and 309 adolescents. Adults experienced more adverse reactions requiring injectable epinephrine, both during in-clinic up-dosing (49% vs. 15.9% and 26.5% for children and adolescents, respectively, p < 0.0001) and during home treatment (22.9% vs. 12.4%, p = 0.007 for children, and 17.5%, p = 0.23 for adolescents). Most adults (61.5%) were fully desensitized, but the rates of full desensitization were significantly lower than children (73.4%, p = 0.013). Significantly more adults (28.3%) undergoing milk OIT failed treatment than children (14.3%, p = 0.015) and adolescents (14.1%, p = 0.022), while failure rates in adults undergoing OIT for other foods were low (9.3%) and comparable with children and adolescents.

OIT is successful in desensitizing most adults with IgE-mediated food allergy. Adults undergoing milk OIT are at increased risk for severe reactions and for OIT failure while failure rates in adults undergoing OIT for other foods are low.

Immunotherapy for food-allergic patients has been effective in inducing desensitization in some populations, but long-term tolerance has remained an elusive target. A challenge facing our field is how to differentiate immune markers that are impacted by immunotherapy from those that are critical biomarkers of tolerance. Data from recent clinical trials have identified several biomarkers and mechanisms for achieving tolerance. These biomarkers include younger age, lower food-specific IgE, lower food component-specific IgE, specific linear epitope profiles, and subsets of food-specific CD4+ T cells. Additional biomarkers under investigation for their relevance in tolerance induction include TCR repertoires, gastrointestinal and skin microbiome, and local tissue immunity. This mini-review highlights recent advances in understanding biomarkers and mechanisms of tolerance induction in food immunotherapy and how these are influencing clinical trial development.

Allergic rhinitis (AR) is frequent in children and adolescents and can severely affect their lives. This article describes the development and validation of a questionnaire to assess treatment needs and benefits in children and adolescents, the PBI-AR-K, in a sample of patients receiving grass pollen sublingual immunotherapy.

The PBI-AR-K was developed based on an open survey including children and adolescents and expert consensus between methodologists, patients, and physicians. The PBI-AR-K assesses patient needs before the treatment and perceived benefit during or at the end of a treatment. A weighted benefit score can be calculated ranging from 0 to 4 (4 = highest possible benefit). The validation was conducted in children (5-12 years) and adolescents (13-17 years) receiving sublingual immunotherapy. Subscales were developed based on factor analysis. Psychometric properties of items and scales were assessed with descriptive statistics, internal consistency, and convergent validity.

The final PBI-AR-K consists of 19 items. For validation, data from 345 patients (mean age 11.1; 60.9% male; n = 223 children; n = 122 adolescents) was analysed. Factor analyses resulted in four subscales for children and three subscales for adolescents. The items with the highest importance ratings were about choice of leisure activities (mean value in children: 3.5) and about being free of AR symptoms (adolescents: 3.3). The weighted PBI-AR-K scores reflected considerable patient-reported benefit (2.08-2.82) in both children and adolescents. Internal consistency of all scales was good or acceptable. In the children's sample, the global scale and three of four subscales were quite consistently correlated with convergent variables, while the subscale 'treatment burden' was significantly correlated only with change in average impairments due to rhinitis symptoms. The adolescents' sample showed more inconsistent results with only change in rhinitis severity being significantly associate with all subscales.

The newly developed PBI-AR-K is a reliable and valid questionnaire for use in children; for the use in adolescents, it should be further elaborated.

Most patients with allergic rhinitis are polysensitized. The efficacy of house dust mite (HDM) allergen immunotherapy (AIT) compared between monosensitized and polysensitized patients remains limited.

To systematically review the efficacy and safety of HDM AIT compared between monosensitized and polysensitized patients with allergic rhinitis.

We searched PubMed/MEDLINE, Scopus, EMBASE, and the Cochrane central register of Controlled Trials (CENTRAL) until June 2022. The primary outcome was the changes from baseline in total nasal symptom score (TNSS). Secondary outcomes were changes from baseline in total medication score (TMS), combined symptom medication score (CSMS), visual analog scale (VAS), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score, immunological parameters, and adverse events (AEs).

Of 13 eligible studies, 10 prospective cohorts, 2 retrospective cohorts, and 1 matched cohort, we identified 10 studies for quantitative synthesis. There were 1,113 patients with allergic rhinitis, 566 with HDM monosensitization and 547 with polysensitization to HDM and other allergens. There was no significant difference in the pooled mean changes of the 2 groups in TNSS (SMD -0.05, 95%CI: -0.22 to 0.11, p = 0.532) and VAS (SMD -0.20, 95%CI: -0.42 to 0.01, p = 0.060) with moderate certainty of evidence. The changes in TMS, CSMS, and RQLQ were similar between the 2 groups with very low certainty of evidence. The AEs were mild and comparable between the 2 groups. The immunological indices remained inconsistent and were not predictive of clinical responses.

A single HDM AIT similarly improved clinical outcomes in monosensitized and polysensitized patients with allergic rhinitis.

The 21st century has seen the propulsion of research in the field of food allergy, which has driven real changes in the clinical approach. Allergen immunotherapy has been recommended for the active management of food allergy. Data have shown promising additional methods of treatment, including biologics. Efforts have been devoted to the risk stratification of food allergy and the standardization of the assessment of food-allergic severity. Alternative routes of administration of epinephrine are under investigation to minimize any mechanical issue and the fear of injections. Evidence-based guidelines have been published by the main international societies in the field of anaphylaxis and food allergy management and new updates are in preparation. In the coming years, treatment options that are currently in pre-clinical or early clinical evaluation will hopefully lead to safe and effective disease-modifying therapies for food allergy in clinical practice. The identification of reliable biomarkers and the standardization of definitions and measurement approaches, alongside a shared decision-making with patients and families, will be key for the development of personalized care and to help minimize the substantial burden of food allergy.

Oral immunotherapy (OIT) an effective treatment for children with persistent food allergy, has concerns about its safety, including Eosinophilic Esophagitis (EoE). The aim of this study was to evaluate the prevalence of EoE in a large cohort of children who underwent OIT in our center. and to determine if there were any clinical, endoscopic or histologic differences depending on the food employed for the OIT.

A retrospective study was performed over a 15-year period (2005-2020). Children who underwent cow's milk (CM), egg and/or peanut OIT and developed EoE were included.

607 OIT were carried out (277 CM-OIT, 322 egg-OIT and 8 peanut-OIT). Seventeen patients (2.8%) had a confirmed histologic diagnosis of EoE with a higher prevalence for patients who underwent CM-OIT (3.9%) than egg-OIT (2.2%). Symptoms suggestive of EoE and a confirmed diagnosis occurred at median times of 25 months and 36 months respectively after the build-up phase of the OIT was completed. Choking, abdominal pain and dysphagia were the most frequent symptoms and lamina propria fibrosis was observed in 41.2% of patients. No significant differences in clinical symptoms, endoscopic or histologic findings between patients under CM or egg-OIT were found. One third of patients reported mild symptoms suggestive of EoE before the OIT.

EoE appears to be a rare but important adverse event that can occur even years after OIT. Validated questionnaires to screen EoE before the OIT and in the follow-up of these patients may be the main tool for an early diagnosis.An infographic is available for this article at: http://links.lww.com/MPG/C952.